Antibodies which bind to the human CC chemokine receptor 4 and uses thereof

Abstract

The present invention provides antibodies which bind to an epitope in the extracellular domain of human CC chemokine receptor 4 (CCR4) and which are capable of inhibiting the binding of macrophage-derived chemokine (MDC) and/or thymus and activation regulated chemokine (TARC) to CCR4. Also provided are inter alia immunoconjugates and compositions comprising such antibodies and methods and uses involving such antibodies, particularly in the medical and diagnostic fields.

The invention claimed is: 
     
       1. An antibody which binds to human CC chemokine receptor 4 (CCR4) and which is capable of inhibiting the binding of macrophage-derived chemokine (MDC) and/or thymus and activation regulated chemokine (TARC) to CCR4, and which comprises at least one heavy chain variable region that comprises three CDRs and at least one light chain variable region that comprises three CDRs,
 wherein said heavy chain variable region comprises 
 
       (i) a variable heavy (VH) CDR1 that has the amino acid sequence of SEQ ID NO: 1, 
       (ii) a variable heavy (VH) CDR2 that has the amino acid sequence of SEQ ID NO: 2, and 
       (iii) a variable heavy (VH) CDR3 that has the amino acid sequence of SEQ ID NO: 20;
 and wherein said light chain variable region of said antibody comprises: 
 
       (iv) a variable light (VL) CDR1 that has the amino acid sequence of SEQ ID NO: 22; 
       (v) a VL CDR2 that has the amino acid sequence of SEQ ID NO: 5; and 
       (vi) a VL CDR3 that has the amino acid sequence of SEQ ID NO: 24. 
     
     
       2. An antibody which binds to human CC chemokine receptor 4 (CCR4) and which is capable of inhibiting the binding of macrophage-derived chemokine (MDC) and/or thymus and activation regulated chemokine (TARC) to CCR4 wherein said antibody has a VH domain having the sequence of SEQ ID NO: 39 and/or a VL domain having the sequence of SEQ ID NO: 40. 
     
     
       3. An antibody according to  claim 1 , wherein said antibody is a fully human antibody. 
     
     
       4. The antibody according to  claim 1 , wherein said antibody is an IgG antibody. 
     
     
       5. The antibody according to  claim 1 , wherein said antibody has a glycosylation pattern which is beneficial for therapeutic application of the antibodies. 
     
     
       6. The antibody according to  claim 1 , wherein at least 10% of the total complex N-glycoside-linked sugar chains bound to the Fc region of said antibody are sugar chains in which fucose is not bound to N-acetylglucosamine in the reducing end in the sugar chain. 
     
     
       7. The antibody according to  claim 1 , wherein said antibody is an antigen binding fragment of an antibody. 
     
     
       8. The antibody according to  claim 1 , wherein said antibody is an antigen binding fragment of an antibody selected from a Fab′, Fab, F(ab′) 2 , single domain antibody, TandAbs dimer, Fv, scFv, dsFv, ds-scFv, Fd, linear antibody, minibody, diabody, bispecific antibody fragment, bibody, tribody, sc-diabody, kappa(lamda) body, BiTE, DVD-Ig, SIP, SMIP or DART. 
     
     
       9. The antibody  claim 1 , wherein said antibody is attached to a therapeutic or diagnostic agent. 
     
     
       10. The antibody  claim 1 , wherein said antibody is attached to a therapeutic or diagnostic agent selected from a radiotherapeutic agent, chemotherapeutic agent, anti-angiogenic agent, apoptosis-inducing agent, anti-tubulin drug, anti-cellular or cytotoxic agent, steroid, cytokine antagonist, cytokine expression inhibitor, chemokine antagonist, chemokine expression inhibitor, anti-inflammatory corticosteroid or NSAIDs, coagulant or anti-viral agent. 
     
     
       11. A pharmaceutical composition comprising an antibody according to  claim 1  and a pharmacologically acceptable excipient, diluent or carrier. 
     
     
       12. A pharmaceutical composition comprising an antibody according to  claim 1  and a pharmacologically acceptable excipient, diluent or carrier, further comprising at least a second therapeutic agent. 
     
     
       13. The antibody according to  claim 1 , wherein said antibody is an IgG 1  antibody.